Pharmacokinetics, placenta, and brain uptake of paclitaxel in pregnant rats

Abstract

Today, cancer incidence during pregnancy is increasing as women delay childbearing until later in life. Therefore, chemotherapy is regularly administered in pregnant women with cancer. In the present study, we evaluated the change in the pharmacokinetics and the fetus distribution of paclitaxel during pregnancy using pregnant rats. Pharmacokinetic parameters, placenta, and brain transport of [H-3]paclitaxel were investigated in nonpregnant or pregnant rats using single intravenous injection technique. The plasma pharmacokinetics of paclitaxel in pregnant rats was markedly different compared with nonpregnant rats. The V (dss) and CL of paclitaxel in pregnant rats were increased, and AUC was decreased compared with nonpregnant rats. The fetus uptake of paclitaxel is markedly lower than the placenta uptake. Paclitaxel is a substrate of P-glycoprotein (P-gp), so P-gp would affect the transport of paclitaxel to the fetus. The brain uptake of [H-3]paclitaxtel was about twofold lower than that of nonpregnant rats. Current findings are important when considering cancer treatment with paclitaxel during pregnancy.